Aims/hypothesis: The aim of this study was to prospectively and longitudinally investigate maternal iron status during early to mid-pregnancy, and subsequent risk of gestational diabetes mellitus (GDM), using a comprehensive panel of conventional and novel iron biomarkers. Methods: A case–control study of 107 women with GDM and 214 controls (matched on age, race/ethnicity and gestational week during blood collection) was conducted within the the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singleton Cohort (2009–2013), a prospective and multiracial pregnancy cohort. Plasma hepcidin, ferritin and soluble transferrin receptor (sTfR) were measured and sTfR:ferritin ratio was derived, twice before GDM diagnosis (gestational weeks 10–14 and 15–26) and at weeks 23–31 and 33–39. GDM diagnosis was ascertained from medical records. Adjusted ORs (aORs) for GDM were estimated using conditional logistic regression analysis, adjusting for demographics, prepregnancy BMI and other major risk factors. Results: Hepcidin concentrations during weeks 15–26 were 16% higher among women with GDM vs controls (median 6.4 vs 5.5 ng/ml; p = 0.02), and were positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.61 (1.07, 6.36). Ferritin levels were also positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.43 (1.12, 5.28) at weeks 10–14 and 3.95 (1.38, 11.30) at weeks 15–26. The sTfR:ferritin ratio was inversely related to GDM risk; the aOR (95% CI) for highest vs lowest quartile was 0.33 (0.14, 0.80) at weeks 10–14 and 0.15 (0.05, 0.48) at weeks 15–26. Conclusions/interpretation: Our findings suggest that elevated iron stores may be involved in the development of GDM from as early as the first trimester. This raises potential concerns for the recommendation of routine iron supplementation among iron-replete pregnant women.
Bibliographical noteFunding Information:
We would like to acknowledge the research teams at our participating clinical centres, including Christiana Care Health Systems, Wilmington, DE, USA; University of California, Irvine, CA, USA; Long Beach Memorial Medical Center, CA, USA; Northwestern University, Evanston, IL, USA; Medical University of South Carolina, Charleston, SC, USA; Columbia University, New York, NY, USA; New York Hospital Queens, NY, USA; St Peters? University Hospital, New Brunswick, NJ, USA; University of Alabama at Birmingham, AL, USA; Women and Infants Hospital of Rhode Island, Providence, RI, USA; Fountain Valley Regional Hospital and Medical Center, CA, USA; and Tufts University, Medford, MA, USA. We would also like to thank the C-TASC Corporation, Owings Mill, MD, USA for providing data coordination, as well as the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA, for providing the laboratory support and resources for the analysis of blood samples and biomarkers. Some of the data from this study were presented as a poster at the 76th Scientific Sessions of the ADA, New Orleans, LA, USA (2016). This research was supported by NICHD intramural funding and included American Recovery and Reinvestment Act funding via contract numbers: HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C and HHSN275201000001Z.
- Gestational diabetes mellitus
- Iron overload
- Soluble transferrin receptor
- sTfR:ferritin ratio